67GaDOTA-α-MSH: Specific melanoma molecular imaging agent

Objectives Melanoma’s incidence and mortality is increasing. The development of a melanoma selective radiotracer would benefit melanoma diagnosis and treatment monitoring. Ga-67 is a scintigraphic imaging radionuclide that is widely available. In this study, a cyclized alpha-melanocyte stimulating hormone (α-MSH) analog with high stability and affinity for the MC1R receptor (over expressed on melanoma cells) was labeled with Ga-67 and was evaluated as a specific melanoma imaging agent

Methods The 67Ga-DOTA-α-MSH synthesis was performed through direct labeling of DOTA-α-MSH with a solution of 67GaCl3 (pH 5) incubated for 30 minutes at 95 °C. The physicochemical controls were performed by reverse phase HPLC with a C18 column and monitor by UV and gamma detectors. The in-vitro radiochemical stability of the radiolabeled peptide was analyzed at 1, 2 and 24 h. Biodistribution studies and scintigraphic imaging were performed in normal mice and B16F10 melanoma tumor bearing C57BK mice.

Results Radiochemical purity of 67Ga-DOTA-α-MSH was >95%. In vitro radiochemical stability of the radiolabeled was >90% up to 24h. Biodistribution studies in normal and tumor bearing C57BK mice performed at 1 h post injection showed renal elimination of the radiolabeled peptide without significant uptake by other organs. Biodistribution performed at 1 h post injection in melanoma bearing mice showed significant melanoma uptake with a “tumor-to-non-tumor” ratio >7. Scintigraphic images performed 1 h post injection of 67Ga-DOTA-α-MSH in C57BK melanoma tumor bearing mice, showed high tumor uptake without any significant uptake by other organs or tissues.

Conclusions 67Ga-DOTA-α-MSH can be considered a specific melanoma targeting agent with potential role in staging, follow up and evaluating response to therapy of melanoma. This preliminary results paths the way to its clinical evaluation.

Research Support ANII, PROINBIO, PEDECIBA.